An efficient synthesis of 4,6-dihydrospiro[azepino[4,3,2-cd]indole-3,3′-indoline]-2′,5(1H)-diones via multi-component reaction

A facile and efficient one-pot three-component synthesis of spiroazepinoindolones has been developed. Using DMF as solvent without any additional acid or metal catalysts, the three-component reaction of readily available isatins, indolamines, and Meldrum's acid affords a new class of spiroheterocycles in moderate yield.     

An Efficient Synthesis of Spiroquinoxalinones via Tandem Reactions

A mild and efficient synthesis of spiroquinoxalinones via tandem condensation of chlorooxoindoline 1 with benzene‐1,2‐diamines 2 is described. And a plausible mechanism for the reaction is proposed.     

Brain-derived neurotrophic factor modulation of Kv1.3 channel is disregulated by adaptor proteins Grb10 and nShc

Background

Developmental dyslexia is a specific cognitive disorder in reading acquisition that has genetic and neurological origins. Despite histological evidence for brain differences in dyslexia, we recently demonstrated that in large cohort of subjects, no differences between control and dyslexic readers can be found at the macroscopic level (MRI voxel), because of large variances in brain local volumes. In the present study, we aimed at finding brain areas that most discriminate dyslexic from control normal readers despite the large variance across subjects. After segmenting brain grey matter, normalizing brain size and shape and modulating the voxels' content, normal readers' brains were used to build a 'typical' brain via bootstrapped confidence intervals. Each dyslexic reader's brain was then classified independently at each voxel as being within or outside the normal range. We used this simple strategy to build a brain map showing regional percentages of differences between groups. The significance of this map was then assessed using a randomization technique.

Results

The right cerebellar declive and the right lentiform nucleus were the two areas that significantly differed the most between groups with 100% of the dyslexic subjects (N = 38) falling outside of the control group (N = 39) 95% confidence interval boundaries. The clinical relevance of this result was assessed by inquiring cognitive brain-based differences among dyslexic brain subgroups in comparison to normal readers' performances. The strongest difference between dyslexic subgroups was observed between subjects with lower cerebellar declive (LCD) grey matter volumes than controls and subjects with higher cerebellar declive (HCD) grey matter volumes than controls. Dyslexic subjects with LCD volumes performed worse than subjects with HCD volumes in phonologically and lexicon related tasks. Furthermore, cerebellar and lentiform grey matter volumes interacted in dyslexic subjects, so that lower and higher lentiform grey matter volumes compared to controls differently modulated the phonological and lexical performances. Best performances (observed in controls) corresponded to an optimal value of grey matter and they dropped for higher or lower volumes.

Conclusion

These results provide evidence for the existence of various subtypes of dyslexia characterized by different brain phenotypes. In addition, behavioural analyses suggest that these brain phenotypes relate to different deficits of automatization of language-based processes such as grapheme/phoneme correspondence and/or rapid access to lexicon entries.     

Synthesis of 3,5-Bis(trifluoromethyl)phenyl-Substituted Pyrazole Derivatives as Potent Growth Inhibitors of Drug-Resistant Bacteria

Enterococci and methicillin-resistant S. aureus (MRSA) are among the menacing bacterial pathogens. Novel antibiotics are urgently needed to tackle these antibiotic-resistant bacterial infections. This article reports the design, synthesis, and antimicrobial studies of 30 novel pyrazole derivatives. Most of the synthesized compounds are potent growth inhibitors of planktonic Gram-positive bacteria with minimum inhibitory concertation (MIC) values as low as 0.25 µg/mL. Further studies led to the discovery of several lead compounds, which are bactericidal and potent against MRSA persisters. Compounds 11, 28, and 29 are potent against S. aureus biofilms with minimum biofilm eradication concentration (MBEC) values as low as 1 µg/mL.     

High-dimensional time series prediction using kernel-based Koopman mode regression

This paper investigates the nonlinear dynamics of a doubly clamped piezoelectric nanobeam subjected to a combined AC and DC loadings in the presence of three-to-one internal resonance. Surface effects are taken into account in the governing equation of motion to incorporate the associated size effects at nanoscales. The reduced-order model equation (ROM) is obtained based on the Galerkin method. The multiple scales method is applied directly to the nonlinear equation of motion and associated boundary conditions to obtain the modulation equations. The equilibrium solutions of the modulation equations and the dynamic solutions of the ROM equation are investigated in the case of primary and principal parametric resonances of the first mode. Stability, bifurcations and frequency response curves of the nanobeam are investigated. Dynamic behaviors of the motion are shown in the form of time traces, phase portraits, Poincare sections and fast Fourier transforms. The results indicate rich dynamic behaviors such as Hopf bifurcations, periodic and quasiperiodic motions in both directly and indirectly excited modes illustrating the influence of modal interactions on the response.     

Comparison of the Newtonian and relativistic predicted trajectories for a low-speed periodically delta-kicked system

The dynamics of a periodically delta-kicked Hamiltonian system moving at low speed (i.e., at speed much less than the speed of light) is studied numerically. In particular, the trajectory of the system predicted by Newtonian mechanics is compared with the trajectory predicted by special relativistic mechanics for the same parameters and initial conditions. We find that the Newtonian trajectory, although close to the relativistic trajectory for some time, eventually disagrees completely with the relativistic trajectory, regardless of the nature (chaotic, nonchaotic) of each trajectory. However, the agreement breaks down very fast if either the Newtonian or relativistic trajectory is chaotic, but very much slower if both the Newtonian and relativistic trajectories are nonchaotic. In the former chaotic case, the difference between the Newtonian and relativistic values for both position and momentum grows, on average, exponentially. In the latter nonchaotic case, the difference grows much slower, for example, linearly on average.     

Tuned Cationic Dendronized Polymer: Molecular Scavenger for Rheumatoid Arthritis Treatment

Cell‐free deoxyribonucleic acid (cfDNA) released from either dead or damaged cells serves as a key autoantigen in rheumatoid arthritis (RA). They can be recognized by nucleic acid (NA) sensors such as the toll‐like receptor (TLR), leading to activation of the innate immune system and chronic inflammation. Developed here is a cationic molecular scavenger, by screening cationic dendronized polymers, which eliminates cfDNA and inhibits TLR recognition and nucleic‐acid‐induced inflammation. The structure–property study demonstrates that toxicity, NA binding capacity, and biodistribution could be balanced to achieve maximum therapeutic effect by exquisite control of the molecular structure. In addition, the optimized cationic polymer effectively inhibited joint swelling, synovial hyperplasia, and bone destruction in collagen‐induced arthritis (CIA) rat models. The results offer support for synthetic polymers offering new paradigm in autoimmune disease treatment.     

Process monitoring of powder pre-paste laser surface alloying

Instead of the continuous powder delivery method using a powder feeder for thick layer laser cladding, pre-pasting of the alloying powder on the substrate is a widely used method to supply the coating powders into the melt pool for LSA. A method to monitor the process of laser surface alloying based on the infrared emission from the melt pool using infrared photodiodes was developed. The technique is solely aimed at the process of laser surface alloying using pre-paste metal powder on the substrate surface prior to laser melting. This monitoring technique is able to distinguish the existence or the absence of the pre-paste powder and the consistency of the laser surface alloying process. The technique is of low cost and is simple to implement into the process.     

Some addition reactions of pentafluorothiophenol and pentafluorobenzenesulfenyl chloride

The addition reactions of pentafluorothiophenol, C₆F₅SH, and pentafluorobenzenesulfenyl choloride, C₆F₅SCl, with various unsaturated systems, including alkenes, alkynes, oxiranes, thiiranes, diazo compounds, aldehydes, ketones, and nitriles have been examined. The physical properties of the new compounds are reported together with some spectroscopic data.